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Biomedical subjects

U Hegerl

Publications and source records attributed to U Hegerl.

At least 73 records · Page 4Linked to original sources
PubMed2000

Identifying psychiatric patients with serotonergic dysfunctions by event-related potentials.

The increasing knowledge concerning anatomical structures and cellular processes underlying event-related potentials (ERP) as well as methodological advances in ERP data analysis (e.g. dipole source analysis) is beginning to bridge the gap between ERP and neurochemical aspects. Reliable indicators of the serotonin system are urgently needed because of its role in pathophysiology and as target of pharmacotherapeutic interventions in psychiatric disorders. Converging arguments from preclinical and clinical studies support the hypothesis that the loudness dependence of the auditory evoked N1/P2-response (LDAEP) is regulated by the level of central serotonergic neurotransmission. Dipole source analysis represents an important methodological advance in this context, because the two N1/P2-subcomponents, generated by the primary and secondary auditory cortex known to be differentially innervated by serotonergic fibres, can be separated. A pronounced LDAEP of primary auditory cortices is supposed to reflect low central serotonergic neurotransmission, and vice versa. LDAEP is a parameter with potential clinical value since subgroups of patients with a serotonergic dysfunction can be identified and can be treated more specifically. In depressed patients, a significant relationship between strong LDAEP, indicating low serotonergic function, and a favourable response to SSRI has been found. Additionally, there is evidence from several studies with patients with affective disorders that a strong LDAEP predicts favourable response to a preventive lithium treatment.

Antimanic Agents↗
PubMed2000

Clinical and biological findings in a case with 48-hour bipolar ultrarapid cycling before and during valproate treatment.

BACKGROUND: The rare cases of patients with 48-hour ultrarapid cycling allow close investigation of mood cycles in affective disorders, because rhythmic changes in psychopathologic state and biological parameters happen very precisely. METHOD: A 67-year-old white man who had experienced bipolar 48-hour ultrarapid cycling (DSM-IV 296.80) for several years was studied without any medication and then again studied 4 weeks later during treatment with valproate (1800 mg/day). RESULTS: Objective and self ratings revealed pronounced manic states 1 day and depressed states the following day, which were found to be accompanied by rhythmic fluctuations in behavior and electroencephalographic parameters, blood cortisol and growth hormone levels (both elevated on depressive days), and urinary metanephrine (dopamine metabolite) and norepinephrine levels (both elevated on manic days). Using single photon emission computed tomography, regional blood flow in the left thalamus was lower than in the right thalamus on the manic day, while symmetric perfusion of the thalamus was found on the depressive day. Under valproate treatment, the patient remitted completely, and significant rhythmic changes in most of the biological parameters were no longer detectable. CONCLUSION: The biological findings in this patient with bipolar 48-hour ultrarapid cycling, which correspond to those in other types of affective disorders, suggest that disturbances in the diencephalon-pituitary axis may be especially correlated to pathologic changes of mood.

Aged↗
PubMed2000

[The Japanese version of the serotonin syndrome scale (JSSS)].

The serotonin(5-HT) syndrome(SS) is a condition of both the central and peripheral 5-HTergic hyperstimulation, characterized by a constellation of 5-HT-related side effects(confusion, agitation, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering or tremor in the setting of the recent addition of 5-HTergic agents. The SS is produced most often by the concurrent use of monoamine oxidase inhibitors and other 5-HTergic agents. However, more recent reports suggest that the tricyclic antidepressant or selective serotonin reuptake inhibitor(SSRI) monotherapy induces the SS. Recently, for the operationalized assessment of both the presence and the severity of the core symptoms of the SS, Hegerl et al. developed the Serotonin Syndrome Scale(SSS) as a modification of the diagnostic criteria of the SS proposed by Sternbach. Since, in Japan, some novel 5-HTergic agents have been, and will be in use, recognition of the SS is quite important. Therefore, for clinical application of SSS, we prepared the Japanese-language version (JSSS).

Diagnostic Techniques, Neurological↗
PubMed2000

Is the EEG helpful in diagnosing and monitoring lithium intoxication? A case report and review of the literature.

Lithium is potentially toxic to the central nervous system. Clinical lithium neurotoxicity may appear at any time during therapy and may go unrecognized. Failure to appreciate this fact leads to delays in diagnosis and treatment, placing the patient at risk of permanent neurological damage or death. In spite of a largely clinical diagnosis of lithium intoxication, the EEG provides an objective criterion of intoxication. We report a case of lithium intoxication with neurotoxic symptoms associated with marked EEG changes despite moderate lithium serum levels. In contrast to the interindividually varying EEG changes under uncomplicated lithium therapy, pathological EEG findings are the rule in the case of intoxication. Several reports evince a closer relationship between neurotoxic symptoms with EEG changes than with serum levels of lithium. This is of clinical interest with respect to intoxication under therapeutic lithium serum levels, since the EEG is the only examination indicating an intoxication. In patients with intoxication, the phenomenon of long-lasting EEG changes after discontinuation of lithium is discussed with respect to neuronal storing of lithium and persisting neurological disturbances.

Aged↗
PubMed1999

[Depression and suicidal behavior more effectively controlled by a team approach. Pilot project to optimize diagnosis and therapy].

The aim of the competition (Specialist-field Networks in Medicine "MedNet") announced by the Federal Ministry for Education and Research (BMBF) is to stimulate the creation of supraregional networks for specific diseases, in order, in this way, to improve cooperation and the transfer of knowledge between research institutions and various levels of medical care. The MedNet "Depression, Suicidal tendency" is one of the winners of this BMBF competition". In view of the central role played by the family doctor in the care given to patients with depressive disorders, permanent improvement in cooperation between physicians in private practice and the research institutions is a central aspect of the planned MedNet activities.

Depressive Disorder↗
PubMed1999

[Drug treatment of obsessive-compulsive disorder. With proper drugs and some patience many patients can be helped].

Pharmacotherapy which, together with behavior therapy, is a major pillar in the treatment of obsessive-compulsive disorder (OCD), can bring about a distinct symptomatic improvement in 50-70% of the patients. In addition to the classical tricyclic antidepressant, clomipramine, a number of new selective serotonin reuptake inhibitors have now been approved for the treatment of OCD. In comparison with depression, pharmacotherapy of OCD is characterized by a long latency of effect of eight to twelve weeks, and by the high doses required by some patients. A combination of pharmacotherapy and behavior therapy is superior to behavior therapy alone, in particular in the case of patients with predominantly obsessive thoughts and additional symptoms of depression. In the case of aggregation with the Tourette syndrome or schizotypal personality disorders, the additional administration of a neuroleptic is recommended. Open studies and case histories have reported good results with pimozide, haloperidol, clozapine and risperidone.

Behavior Therapy↗
PubMed1999

Digitized analysis of handwriting and drawing movements in healthy subjects: methods, results and perspectives.

The diagnosis of movement disorders and the distinction between their possible generation by drug-treatment or illness can be done more objectively by using digitized analyses of hand movements. The aim of this study was to define this method, that is to identify its reliability and the influence of several covariables upon measurements, in healthy subjects. Simple writing and drawing tests were administered, using a digitizing tablet, transmitting signals to a computer for processing. The kinematic parameters identified in this way provided objective, reliable and valid measures for the dynamics and the degree of automation of hand movements. Analysis of the data showed that younger subjects write faster and with a higher degree of automation than older subjects. Other moderating variables, such as verbal intelligence and customary motor activity in everyday life (motoric practice) could be identified, whereas personality and gender were found to have little influence. There were no significant differences between left-handers and right-handers in hand movements. The movement parameters had a high test retest stability. The results of this study in healthy subjects indicate that age, verbal intelligence and motor practice should be considered when evaluating the effects of drug-treatment or psychiatric illness upon hand-movement in patients.

Adult↗
PubMed1999

Late auditory evoked potentials (P300) do not discriminate between subgroups of alcohol-dependent patients defined by family history and antisocial personality traits.

Alcohol dependent patients with a family history of alcoholism and with antisocial personality traits were supposed to have frontal brain dysfunction. Late evoked potentials may be useful to discriminate these patients from patients without family history or antisocial behavior. We investigated 56 abstinent patients hypothesizing that four subgroups of abstinent alcoholics with regard to family history (FHP: family history positive, FHN: family history negative) and antisocial behavior (ASP: antisocial traits present, ASN: antisocial traits not present) would exhibit differences in P300, particularly when recorded by frontal electrodes. FHP/ASP patients were expected to show the lowest P300 amplitudes in frontal electrode sites. Beside single electrode recordings, a new method in analyzing P300 scalp data by dipole source analysis (BESA: Brain electric signal analysis) was used. No difference in the P300 values was observed between the FHP/FHN and ASP/ASN groups. Similar results were found by analyzing ASP/ASN and FHP/FHN groups separately. The findings of single electrode recordings were consistent with BESA-dipole results. In conclusion, auditory P300 had a low discriminative power with regards to subgroups of inpatient alcoholics defined by family history and antisocial personality traits. Reasons for the negative findings in this study are discussed.

Adult↗
PubMed1999

P300 subcomponents reflect different aspects of psychopathology in schizophrenia.

BACKGROUND: The aim of the study was to investigate abnormalities of P300 subcomponents in schizophrenic patients as well as relationships between these subcomponents and positive versus negative schizophrenic symptoms. METHODS: Nineteen schizophrenic patients and 19 healthy controls were tested with an auditory event-related potential oddball paradigm designed to elicit the P300. The P300 data were analyzed by separating P300 subcomponents with a recently developed dipole source model. RESULTS: Compared to healthy controls, schizophrenic patients showed reduced P300 amplitudes of the temporo-basal dipoles, corresponding mainly to P3b. Positive symptoms of the Positive and Negative Syndrome Scale correlated positively with the temporo-basal but not with temporo-superior dipole P300 activities, whereas negative symptoms correlated positively with the temporo-superior but not with temporo-basal dipole activities. CONCLUSIONS: The P300 subcomponents separated with the dipole model are affected in a different manner by positive versus negative symptoms. Furthermore, the positive correlation between the severity of psychopathology and the P300 amplitudes of the different dipole activities appears to be a state-dependent effect, which has to be separated from the P300 amplitude reduction as a trait marker in schizophrenic patients.

Adult↗
PubMed1999

[Postoperative delirium: risk factors, prophylaxis and treatment].

After surgical operations delirium can occur as a serious and possible lethal complication in about 5-15% of patients. Additionally, risk factors such as old age, polymedication, organic and psychiatric diseases raise the incidence. After open-heart and orthopedic surgery more than half of the patients are affected. Delirium has negative effects on postoperative mobilization and reconvalescence and prolongs treatment on the ward. It is discussed in the literature that delirium may induce dementia in older patients. The correction of metabolic and electrolyte imbalances, as well as the therapy of neurologic and psychiatric diseases, belongs to prophylactic treatment. Environmental conditions which facilitate reorientation of the patient after operation have beneficial effects. Some success has been achieved by using the nootropic substance piracetam as a prophylactic. In acute treatment, the butyrophenon-neuroleptic haloperidol is the drug of choice. In delirium caused by intoxication with anticholinergic agents, physostigmin is indicated. Benzodiazepines, clonidine and clomethiazole are used in particular for the treatment of withdrawal delirium.

Aged↗
PubMed1999

[Limbic ictus as a condition for anxiety attacks].

Episodes of anxiety have been reported to be the most common psychological symptoms in patients with partial seizures. They may occur before, during and after seizures and can also appear in isolation without any convulsive symptoms. The epileptic anxiety syndrome is strikingly similar to panic attacks, and panic disorder is an important differential diagnosis. The close relationship between epileptic seizures and panic attacks is of special interest for a better pathophysiological understanding of panic attacks. In the literature an epileptiform neuronal activity is discussed as a possible underlying mechanism for panic disorder. The finding that anxiety was the most common experiential phenomenon produced by electrical stimulation of amygdala and hippocampus with depth electrodes points in this direction. PET has demonstrated abnormalities of hippocampal structures during the nonpanic state of patients with panic disorder. In addition, some EEG studies have demonstrated a high incidence of epileptiform EEG patterns in patients with panic disorder with or without agoraphobia. This was the reason why several investigators proposed that a subset of panic attacks may be related to abnormal epileptiform neuronal activity in the limbic system. The size of this subset is difficult to determine because discharges in the depth of the limbic system often cannot be seen in the scalp EEG. Concerning the hypothetical pathophysiological mechanism of panic disorder therapeutic measures were taken with antiepileptic agents. The best results were obtained for valproic acid. It seems to be reasonable to make a therapeutic trial with antiepileptic medication after nonresponse to standard pharmacotherapy.

Anxiety Disorders↗
PubMed1999

Corpus callosum size in schizophrenia--a magnetic resonance imaging analysis.

Previous MRI studies have shown differences in corpus callosum size between schizophrenic patients and controls. The corpus callosum (CC), as the main interhemispheric fiber tract, plays an important role in interhemispheric integration and communication. Though MRI studies suggest smaller CC in schizophrenia, there are still conflicting findings. Using in vivo magnetic resonance imaging, it was investigated whether the midsagittal area of CC differs between twenty-three right-handed male schizophrenic patients and twenty-three matched controls. Total CC area, five subregions of CC, total brain volume, gray and white matter were measured. No differences between schizophrenic patients and controls were found regarding all CC measurements, total brain volume, and gray matter tissue. However, a significant reduction of white matter tissue in the patient group emerged. There was no correlation between CC morphology and clinical variables such as age of onset, length of illness or symptom severity. Interestingly, five schizophrenic patients with a positive family history of schizophrenia showed significant reduction of the subregion C3, associated with a reduced total brain and gray and white matter volume. Significant reduction in the CC and its subregions was not confirmed in this group of patients with schizophrenia. In the subgroup of schizophrenic patients with a positive family history of schizophrenia, a significant reduction of the subregion corresponding to a part of the trunk of the CC was found.

Adult↗
PubMed1999

Auditory evoked potentials reflect serotonergic neuronal activity--a study in behaving cats administered drugs acting on 5-HT1A autoreceptors in the dorsal raphe nucleus.

A valid indicator of central serotonergic neurotransmission would be useful for various diagnostic and psychopharmacological purposes in psychiatry. However, known peripheral serotonergic measures only partially reflect serotonergic function in the brain. Previous findings suggest that the intensity dependence of auditory evoked potentials (AEPs) is closely related to central serotonergic activity. The present study examines the effects of microinjection of a 5-HT1A agonist (8-OH-DPAT) and a 5-HT1A antagonist (spiperone) into the dorsal raphe nucleus (DRN) on AEP recorded epidurally from the primary and secondary auditory cortex in behaving cats. We found a stronger intensity dependence only of AEP from the primary auditory cortex after 8-OH-DPAT, which inhibits the firing rate of serotonergic DRN neurons, and a weaker intensity dependence after spiperone, which increases serotonergic cell firing, as compared to baseline measurements. These results demonstrate that the intensity dependence of AEP is inversely related to serotonergic neuronal activity and that it may be a promising tool for assessing central serotonergic function in humans (e.g., identifying patients with low serotonergic neurotransmission).

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Stability of the mismatch negativity under different stimulus and attention conditions.

OBJECTIVE: Mismatch negativities (MMN) elicited by frequency and duration changes in a sequence of repetitive tones were recorded in test and retest sessions from 45 subjects. METHODS: Tones presented with a stimulus onset asynchrony (SOA) of 0.5 s were to be ignored while attention had no instructed focus in one group and was directed to an active visual vigilance task in a second group of subjects. RESULTS: MMN amplitude was larger for duration deviants, the focus of attention had no systematic effect. Individual replicability of the MMN amplitudes was generally better when duration deviants were used. In addition, directing attention to the visual task increased the retest reliability of the duration deviance MMN. In this condition, the test-retest correlation coefficients were above 0.8 at all frontal scalp sites (0.87 at F4). CONCLUSIONS: The study shows that the deviant type as well as the attentional condition may have substantial effects on the stability and replicability of MMN potentials. The choice of the appropriate task condition is essential for using the MMN in group comparisons and as a diagnostic tool in individual cases.

Acoustic Stimulation↗
PubMed1999

[Piracetam in anesthesia for prevention of postoperative delirium].

Delirium is a serious postoperative complication after general anaesthesia. The incidence is estimated to be about 10-15%. In the case of additional risk factors, such as old age, previously existing cerebral-vasculous and psychic deficiencies, and anaesthesia of long duration the incidence is much higher. Delirium impairs postoperative mobilisation and convalescence of the patient, can lead to a longer hospital stay and is associated with higher mortality rates. In a series of clinical studies it could be shown that the perioperative administration of the nootropic piracetam led to a shorter recovery period after anaesthesia and had a favourable influence on the delirious symptoms. Especially patients with risk factors for postoperative delirium profited from prophylactic application of piracetam. The success of this medication can be explained by a protective influence of the substance on central neurons against hypoxia, ischemia and intoxication, all of which are discussed as possible causes for postoperative delirium. Next to the pathogenetic mechanisms of postoperative delirium, the mode of action of piracetam is shown in a review and a summary of references on the clinical use in anaesthesia is given.

Anesthesia, General↗
PubMed1999

Double-blind, randomized, placebo-controlled clinical trial on the efficacy and tolerability of a physostigmine patch in patients with senile dementia of the Alzheimer type.

Owing to the pharmacokinetic properties of physostigmine when administered by conventional routes, long-term cholinergic treatment of Alzheimer's disease is difficult to manage. In order to overcome the problems associated with the oral and intravenous application of physostigmine, and to improve patients' compliance, a transdermal therapeutic system was developed. The efficacy and tolerability of this system were evaluated in a double-blind, randomized, multicenter study comparing patches containing 30 mg and 60 mg physostigmine with a placebo patch. The clinical trial followed the basic principles of the various guidelines on the evaluation of anti-dementia drugs, and included patients with mild to moderate probable Alzheimer's disease. A total of 204 patients with probable Alzheimer's disease were included in the study. Of these, 136 patients were eligible for the according-to-protocol analysis of efficacy, 167 subjects for the intention-to-treat analysis of efficacy, and 181 patients were included in the safety analysis. In contrast to the hypothesis to be tested, the efficacy of physostigmine was not superior to that of placebo after a treatment period of 24 weeks. On the contrary, there was even a slight, but not statistically significant, trend toward a better outcome in the placebo group. Median physostigmine plasma concentrations of approximately 100 pg/ml were measured, showing a high degree of interindividual variability and no linear dose relationship between the 30 mg and 60 mg dosages. Plasma cholinesterase activity was not significantly affected by physostigmine. The physostigmine patch application in doses of 30 mg and 60 mg apparently did not lead to physostigmine plasma concentrations that were sufficient to compensate for cholinergic deficiencies in affected brain areas and produce clinical benefits. Both the drug and the transdermal system were generally well tolerated under the study conditions. Modifications of the patch system may perhaps make it possible to achieve higher physostigmine plasma concentrations, which seem to be required to induce the expected beneficial effects during long-term treatment of Alzheimer's disease.

Administration, Cutaneous↗
PubMed1999

Neurochemical substrates and neuroanatomical generators of the event-related P300.

The present review focuses on the current knowledge of the neurochemical processes and neuronal structures involved in the generation of P300. The increasing knowledge in this area facilitates the physiological interpretation of P300 findings as well as the link between P300 research and other research findings in biological psychiatry. Concerning the question of neurochemical substrates, the glutamatergic, GABAergic, cholinergic, noradrenergic, dopaminergic and serotonergic influences on P300 are reviewed. The knowledge of the generating structures of P300 is summarized from intracranial studies, magnetoencephalographic investigations, lesion and animal studies.

Acetylcholine↗